SynBERC:Chassis
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This is a draft list of research topics that the SynBERC Chassis Thrust is considering for support.
Please feel free to contribute & edit.
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Conference Calls
Chassis Goals
Quantitative specs/measures/milestones
Goal 1 Components to be changed (quantitative goals in parens)
- Pathway removal to free up more promoter types : (# paths = 2)
- Cell heterogeneity -- e.g., ara transporter : (variance x0.7)
- Genetic code changes
- # of codon changes (314 UAG to UAA)
- # of novel phage restistances (10) & resistance level (x100)
- Introduce novel chemistries into cells :
- Amber suppressor efficiency (x1.5)
- # of additional amino acids beyond 21 (+2)
Goal 2 Chassis robust to change & minimizing mutation rates
- Anti-mutator alleles of: dam, dnaEQ, mutDHLMRSTY, oxyR, polAC, recAG, ssb, topB, ung, uvrD, or vsr : (mutation rate x0.5)
- Mutationally inactivate insertion elements & transposons : (mutation rate x0.1) Kristala
Goal 3 Dedicated DNA, RNA & protein synthetic systems
- Isolate exogenous gene function from native chromosome: I/O transfer function for main/plasmid/BAC
- Origin: Partition, Addiction : (loss rate x0.3)
- Improved recombination (x2)
- Dedicated RNA & protein systems: (efficiency >10%, crosstalk <10%)
- Virtual Machines & Demand specifications
Goal 4 Safety controls on the chassis
- Delete phage lysogens & receptors (e.g. LamB) : resistance level (x100)
- Delete surface toxins (Lps) : quant sepsis, innate imm. (x0.1)
- Low conjugation (Express TraS and TraT) : escape rate (x0.1)
- Add complicated or rare auxotrophies to prevent survival outside the lab -- aTc-tetR, Dap : (t1/2 = 1 to 90hr); (escape % x0.01) ChrisV
- Remove antibiotic resistance genes : MIC (x0.1)
Chassis Models
- Translational fidelity and pausing in novel genetic codes
- Recombination and DNA synthesis forks
- Minimal Cells
- Maximal Cells -- combinatorial selections
Chassis support for Testbeds and iGEM
Chassis Characterization, Screening & Tuning
- Test Constructs for Characterization
- Models that Support Data Analysis
- Scaleable Parts & Devices Screening & Selection Platforms
- Sequencing Platforms : Polonies
- Assembly Platform: COG
- Programming Cells Instrumentation: GE-MASS
Societal Impact
- Safety – clinical, accidental, threat A Synthetic Biohazard Non-proliferation Proposal
- Surveillance – International Consortium for Polynucleotide Synthesis (ICPS)